Disopyramide and Azithromycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Disopyramide
Azithromycin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of QT interval prolongation and serious cardiac arrhythmias
Interaction Deep Dive
Use of macrolides, including azithromycin, has been associated with prolonged cardiac repolarization and QT interval. Rare reports of torsades de pointes during azithromycin therapy have occurred during postmarketing surveillance. Although risk appears to be low, concomitant use of azithromycin and a class IA antiarrhythmic, such as disopyramide, should be avoided due to the potential for additive effects on the QT interval and an increased risk of serious cardiac events3. Disopyramide has also been associated with prolongation of the QT interval and may cause exacerbation of arrhythmia, including ventricular tachycardia (VT) and ventricular fibrillation 1. A patient stabilized on disopyramide and metoprolol for 5 years developed VT associated with an elevated disopyramide level 11 days after initiation of azithromycin 2. If concomitant therapy is warranted, closely monitor ECG for QT interval prolongation. If a QRS interval prolongation of greater than 25% occurs, discontinue disopyramide. If a QT interval prolongation of greater than 25% with persistent ectopy occurs, monitor the patient closely and consider discontinuation of disopyramide therapy 1.
Why it happens (mechanism)
Additive QT interval prolongation
Literature reports
1 report — tap to read
a) A case report describes a 35-year-old female who experienced a potentially fatal interaction with azithromycin and disopyramide. The patient began taking disopyramide and metoprolol for vasopressor syncope and was stabilized on this regimen for five years. Azithromycin was initiated when the patient developed a fever and lower abdominal pain. Eleven days after initiation of azithromycin she presented to the emergency room with malaise, lightheadedness, and urinary retention. Ventricular tachycardia (123 beats/min) with left bundle branch morphology was evident on an electrocardiogram. The patient subsequently experienced hypotension and loss of consciousness. Dopamine was initiated and disopyramide levels were 11.1 mg/L. Another electrocardiogram demonstrated junctional rhythm at 87 beats/min, a markedly prolonged QT interval of 560 ms, and anterolateral T wave inversions. An echocardiogram demonstrated diffuse left ventricular dysfunction and was remarkable for an ejection fraction of approximately 0.20. The patient subsequently regained consciousness and required a continuous infusion of dopamine for some time. Despite recovery from arrhythmias, fevers continue to recur in this patient 2.
Common questions
Can I take Disopyramide and Azithromycin together?
An increased risk of QT interval prolongation and serious cardiac arrhythmias Always confirm with your pharmacist or prescriber before making any change.
How serious is the Disopyramide and Azithromycin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Disopyramide or Azithromycin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: NORPACE(R), NORPACE(R) CR oral capsules, extended-release capsules, disopyramide phosphate oral capsules, extended-release capsules. G.D. Searle LLC, Chicago, IL, 2006. DailyMed
- Granowitz E, Tabor K, & Kirchhoffer J: Potentially fatal interaction between azithromycin and disopyramide. PACE 2000; 23:1433-1435. PubMed
- Product Information: ZMAX(R) oral extended-release suspension, azithromycin oral extended-release suspension. Pfizer Inc (per FDA), New York, NY, 2021. DailyMed
Keep reading about Disopyramide
Keep reading about Azithromycin
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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